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EFLA 945 restricts AIM2 inflammasome activation by preventing DNA entry for psoriasis treatment
Cytokine ( IF 3.7 ) Pub Date : 2020-03-01 , DOI: 10.1016/j.cyto.2019.154951
I-Che Chung , Sheng-Ning Yuan , Chun-Nan OuYang , Sheng-I Hu , Hsin-Chung Lin , Kuo-Yang Huang , Wei-Ning Lin , Yu-Ting Chuang , Yu-Jen Chen , David M. Ojcius , Yu-Sun Chang , Lih-Chyang Chen

Psoriasis is a chronic inflammatory skin disease that affects about 2% of the general population. Activation of the Absent in Melanoma 2 (AIM2) inflammasome is crucial for immune defense, but it can also cause inflammatory and autoimmune diseases, including psoriasis. We currently lack an AIM2 inflammasome inhibitor that could be used therapeutically. Here, we show that EFLA 945, a safe product of red grape vine leaf extracts, can restrict AIM2 inflammasome activation. Mechanistically, EFLA945 prevents DNA entry into THP-1-derived macrophages, and thereby inhibits cytoplasmic DNA-dependent apoptosis-associated speck-like protein containing a CARD (ASC) oligomerization, caspase-1 activation, and the secretion of interleukin (IL)-1β and IL-18. The major phytochemicals of EFLA 945, resveratrol and peonidin 3-O-glucoside (P3G), appear to be the potential bioactive compounds responsible for its ability to restrict AIM2-dependent IL-1β secretion. Importantly, in an in vivo mouse model, EFLA 945 attenuates imiquimod (IMQ)-induced psoriasis-related pro-inflammatory responses in topical psoriatic skin, including caspase-1 activation, IL-1β maturation, and IL-17 production, and decreases the severity of psoriasis. Together, these results demonstrate that the safe natural product, EFLA 945, can restrict the AIM2 inflammasome activation through preventing DNA entry and may prove beneficial for treating psoriasis.

中文翻译:

EFLA 945 通过阻止 DNA 进入治疗银屑病来限制 AIM2 炎症小体的激活

银屑病是一种慢性炎症性皮肤病,影响约 2% 的普通人群。激活黑色素瘤 2 (AIM2) 炎症小体对于免疫防御至关重要,但它也可能导致炎症和自身免疫性疾病,包括银屑病。我们目前缺乏可用于治疗的 AIM2 炎症小体抑制剂。在这里,我们展示了 EFLA 945,一种红葡萄藤叶提取物的安全产品,可以限制 AIM2 炎症小体的激活。从机制上讲,EFLA945 阻止 DNA 进入 THP-1 衍生的巨噬细胞,从而抑制细胞质 DNA 依赖性凋亡相关斑点样蛋白,其中包含 CARD (ASC) 寡聚化、caspase-1 激活和白细胞介素 (IL) 的分泌- 1β 和 IL-18。EFLA 945、白藜芦醇和芍药苷 3-O-葡萄糖苷 (P3G) 的主要植物化学物质,似乎是潜在的生物活性化合物,负责其限制 AIM2 依赖性 IL-1β 分泌的能力。重要的是,在体内小鼠模型中,EFLA 945 在局部银屑病皮肤中减弱咪喹莫特 (IMQ) 诱导的银屑病相关促炎反应,包括 caspase-1 激活、IL-1β 成熟和 IL-17 产生,并减少牛皮癣的严重程度。总之,这些结果表明,安全的天然产物 EFLA 945 可以通过阻止 DNA 进入来限制 AIM2 炎症小体的激活,并且可能证明对治疗银屑病有益。包括 caspase-1 激活、IL-1β 成熟和 IL-17 产生,并降低银屑病的严重程度。总之,这些结果表明,安全的天然产物 EFLA 945 可以通过阻止 DNA 进入来限制 AIM2 炎症小体的激活,并且可能证明对治疗银屑病有益。包括 caspase-1 激活、IL-1β 成熟和 IL-17 产生,并降低银屑病的严重程度。总之,这些结果表明,安全的天然产物 EFLA 945 可以通过阻止 DNA 进入来限制 AIM2 炎症小体的激活,并且可能证明对治疗银屑病有益。
更新日期:2020-03-01
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